Previous studies in this laboratory have shown that cell-mediated immune responses are triggered early during the progressive growth of the mastocytoma P815Y and the thymoma EL4 in their syngeneic host DBA/2 and C57BL/6 mice, respectively. As growth progresses, the in vivo growing tumor cells become refractory to the in vivo generated "killer cells," behaving as if they had undergone antigenic modulation. Tumor cells that had been growing in animals for more than 2 weeks were no longer sensitive to cytotoxic action. Recently, we have observed that a humoral response is also triggered in parallel, leading to the finding of specific immunoglobulin (Ig) on the progressively growing tumor cells. The presence of this Ig on the tumor cells prevents the binding of additional amounts of H-2D and K antibody. The Ig has been eluted from the in vivo growth cells, and the eluate has a demonstrated protective effect when animals are primed with this eluate prior to tumor challenge. It is the purpose of this project to investigate the humoral response in depth with the following objectives in mind initially: (1) Is the specific Ig the modulating agent that confers to the progressively growing tumor cells' resistance to the cell-mediated cytolytic effectors? (2) Is the partial protection induced by the eluted Ig to a lethal tumor challenge due to the elicitation of an anti-idiotype antibody response? (3) determine the properties of the cell-surface molecules or complexes that bear the antigenic structures that induced the antitumor immune response; and (4) determine the role that these antigens and the host immune responses play in progressive tumor growth. (MI)